TOTAL SYNTHESIS OF ISOCAULIBUGULONE A AND ANALOGUES

Caulibugulones are alkaloids with remarkable anticancer activity, despite this, a serious drawback is their lack of selectivity and also their high cytotoxicity to normal cells. In order to circumvent this problem, we envisage the synthesis of the isocaulibugulones to better evaluate the structure vs. activity relationship in this case. Thus, the strategy to prepare isocaulibugulones involves the reversal of regioselectivity during the nucleophilic attack to an isoquinoline-5,8-dione, due to its conversion to its N-oxide, changing the electronic control of the substrate.